"King of Bitters" (Andrographis paniculate) Leave Extract: An "Inexpensive" PAK Blocker

Recently a group led by Chris Gasche at Vienna Medical University in Austria found that Mesalamine (5-ASA), an Aspirin derivative, blocks the oncogenic kinase PAK (1). This drug was developed around 1977 for the therapy of bowel ulcers. Since both bowel ulcers and cancers are known to require PAK, I started looking for a series of anti-ulcer drugs, in particular natural and inexpensive products, which are used not only for ulcer, and but also for other PAK-dependent diseases such as cancers (in particular solid tumors), inflammatory diseases such as asthma and arthritis, a variety of infectious diseases such as malaria, AIDs and flu, as well as AD (Alzheimer’s disease) and type 2 diabetes.

To my great surprise, the herb extract called HMPL-004, which is the 90% alcohol-extract of leaves of a Southasian plant called “King of Bitters” (Andrographis paniculata) is more potent than Mesalamine to suppress the bowel ulcer, according to the 2011 clinical trial report from a group led by Bill Sandborn at UCSD in collaboration with a Chinese company (HMPL) in Shanghai (2). 1200 mg of HMPL-004 daily is as effective as 4500 mg of Mesalamine when they are orally administered. Thus, it is most likely that HMPL-004 blocks PAK as Mesalamine. Indeed Andrographolide, a diterpene lactone of MW 350, the major anti-ulcer/anti-cancer ingredient in this extract has been shown to block the oncogenic PI-3 kinase, leading the inactivation of both PAK and AKT (3).

Is this bitter extract available on the market?  Yes, several on-line companies are selling this extract in capsules very inexpensively. 400 mg capsule costs only 10 cents. Ulcer patients need 3-4 capsules daily (costing only 30-40 cents)!  I have previously introduced an inexpensive NZ propolis extract called “Bio 30” for the life-long therapy of NF (neurofibromatosis) which requires PAK. Currently 25 ml bottle of Bio 30 costs around US$7, and since average adults (weighing around 60 kg) need 6-12 ml daily, their daily cost would be US$ 2-4. Thus, compared with Bio 30, this herb extract (called “Chua Xin Lian” in China) is far cheaper. So far at this dose the herb extract causes no side effect. Thus, it would be worth testing the therapeutic effect of HMPL-004 on NF and several other brain diseases such as AD, because it passes the BBB (blood brain barrier).

References:

1. Khare V, Lyakhovich A, Dammann K, Lang M, Borgmann M, Tichy B, Pospisilova S, Luciani G, Campregher C, Evstatiev R, Pflueger M, Hundsberger H, Gasche C. Mesalamine modulates intercellular adhesion through inhibition of p-21 activated kinase-1. Biochem Pharmacol. 2012, in press.  

2.      Tang T, Targan SR, Li ZS, Xu C, Byers VS, Sandborn WJ. Randomised clinical trial: herbal extract HMPL-004 in active ulcerative colitis - a double-blind comparison with sustained release mesalazine. Aliment Pharmacol Ther. 2011, 33:194-202. 

3.      Lee YC, Lin HH, Hsu CH, Wang CJ, Chiang TA, Chen JH. Inhibitory effects of andrographolide on migration and invasion in human non-small cell lung cancer A549 cells via down-regulation of PI3K/Akt signaling pathway. Eur J Pharmacol. 2010, 632: 23-32.